Cannabidiol compositions and uses thereof

ABSTRACT

The present invention is directed to use of cannabidiol and compositions thereof as an anti-bacterial agent against multi-drug resistant bacteria such as  Pseudomonas aeruginosa.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application is a divisional of U.S. application Ser. No.16/306,219, filed Nov. 30, 2018, now U.S. Pat. No. 10,952,432, which isthe U.S. national stage application of International Patent ApplicationNo. PCT/EP2017/063385, filed Jun. 1, 2017.

The Sequence Listing for this application is labeled “Seq-List.txt”which was created on Nov. 26, 2018 and is 3 KB. The entire content ofthe sequence listing is incorporated herein by reference in itsentirety.

FIELD OF THE INVENTION

The present invention relates to the field of antibacterial agents. Inparticular, the invention relates to the use of cannabinoid compositionsas anti-bacterial agent against multi-drug resistant bacteria.

BACKGROUND OF THE INVENTION

Biofilm is a structured microbial community which is a naturallyoccurring form of growth of many microorganisms. Biofilm formation isoften a very rapid process, which includes several phases and involvesconditioning the carrier surface for enabling the initial binding of thecells to the carrier surface through physicochemical interaction,production of binding molecules (e.g. extracellular polymericsubstances, adhesins) for irreversibly anchoring the cells on thecarrier surface, organizing the cell community in the form ofmicrocolonies and formation and maturation of the biofilm architecture(Masák et al., 2014, FEMS Microbiol. Ecol., 89: 1-14). Those steps implysignificant changes in the physiology of the cells often leading tochanges in cell phenotype, the development of new metabolic pathways andthe expression of virulence factors. The deployment of such changes in aunified and coordinated manner between the cells within the colony isachieved through signaling pathways between cells. In the pseudomonads,and in particular the common gram-negative bacterium opportunistic humanpathogen, Pseudomonas aeruginosa, which is involved in nosocomial andlife-threatening infections of immunodepressed patients, thiscell-to-cell communication is realized through a chemically-basedcommunication system called Quorum Sensing (QS). QS was shown to beessential to control the initial host defense and the launch of thevirulent offensive to the host through the coordination of the timelyexpression of a battery of virulence factors with the growth of thecolony and therefore with the biofilm formation process (Masák et al.,2014, supra; Juhas et al., 2005, Environmental Microbiology, 7(4):459-471). Further, in Pseudomonas species, biofilm growth generallyincreases their resistance to various negative environmental influencessince they are metabolically less active within the biofilm and henceless receptive to antimicrobial agents and environmental disruptions. Inaddition, biofilms form a physical barrier against the entry ofantimicrobial agents. Therefore, this increased resistance enables themto inhabit a broad range of niches and colonize the soil matrix, planttissue, etc. (Masák et al., 2014, supra; Rybtke et al., 2015, J Mol.Biol. 427: 3628-3645).

Infections caused by bacterial biofilms of multi-drug resistant (MDR)bacteria, also called nosocomial infections, have become a major concernfor most hospitals and healthcare facilities, since they contribute toan increase in morbidity and mortality compared to the underlyingdiseases alone and impact length of patients' stay and relatedhealthcare costs.

Biofilms have been shown to be the underlying cause of manytissue-associated and implant-associated infections (Rybtke et al.,2015, supra), such as dental and buccal infections such as dentalcaries, periodontitis, otorhinolaryngologic infections such as otitis,in particular chronic otitis media (COM) and chronic sinusitis,respiratory infections such as cystic fibrosis (CF) and pneumonia,especially pneumonia in mechanically ventilated patients, skin infectionsuch as chronic wound infections, musculoskeletal infections, urologicaland/or prostatic track infections, biliary tract infection, native valveendocarditis, opportunistic infections in immunodepressed patients suchas cancer patients (Markou et al., 2014, Frontiers in Cellular andinfection microbiology, 3(115), 1-5) and a range of medicaldevice-related infections. Treatment of infections produced by P.aeruginosa is complicated by the organism's resistance profile and maylead to treatment failure and/or exposing patients to adverse effectsfrom antibiotic drug regimens. Current medications for preventing andtreating those nosocomial infections are extensive antibiotherapy, whichhowever often develops into lethal infections due to the high resistanceof the bacteria to many antibiotics and their shielding by biofilms thatprotect it from the action of both drugs and immune system.Specifically, acute fulminant infections, such as bacteremic pneumonia,sepsis, burn wound infections and meningitis are associated withextremely high mortality.

Further, bacteria biofilm formation constitutes a problem in food andcosmetic formulation contamination (Wong et al., 2000, Journal of Foodprotection, 8, 1015-1153), artwork degradation, water contamination(Barbeau et al., 1996, Appl. Environ. Microbiol., 62(11), 3954-3959) andmedical devices contamination (File et al., 1995, 16(7), 417-418).Various approaches have been developed to regulate/suppress Pseudomonasbiofilm and formation thereof, which may or may not include interferingwith the regulatory mechanisms of biofilm formation. Quorum sensing, dueto its involvement in the expression of several virulence factors andbiofilm formation in P. aeruginosa has been an attractive target for thedesign of novel drugs for the treatment of P. aeruginosa infections(Juhas et al., 2005, supra). Some substances have been presented asbeing able to interfere with the mechanism of quorum sensing (QS) suchas water extracts of rhubarb, Fructus Gardeniae and Andrographispaniculata, cis-2-Dodecenoic acid, garlic, other aqueous extracts ofcommon fruits, herbs, and spices, resveratrol, erythromycin,azithromycin, clarithromycin and spiramycin (Masák et al., 2014, supra).However, none of the currently developed quorum sensing inhibitors has auniversal utilization and may require an appropriate approach dependingon the site where the biofilm is formed (Masák et al., 2014, supra).

Cannabidiol (CBD) is a type of cannabinoid found as a major constituentof the cannabis plant, especially Canabis sativa (Asthton, 2001, BritishJournal of Psychiatry, 178, 101-106). CBD has been described as anon-psychoactive substance having potential medical applications in thetreatment of disorders such as epilepsy, multiple sclerosis spasms,anxiety disorders, schizophrenia, nausea, convulsion and inflammation,as well as inhibiting cancer cell growth. CBD, pre-CBD as well as thesynthetic abnormal CBD (abn-CBD) have been described as having activityagainst a variety of methicillin-resistant Staphylococcus aureus (MRSA)strains (Appendino et al., 2008, J. Nat. Prod., 71: 1427-1430).

Due to the severity of infections and contaminations due toGram-negative bacteria such as P. aeruginosa, the increasing resistanceof those bacteria to current antibiotic medications and the high risk ofsome patients to catch such infections, it would be highly desirable tohave new methods for preventing and/or treating Gram-negative bacteriarelated infections, such as nosocomial infections.

SUMMARY OF THE INVENTION

The present invention relates to the unexpected finding that cannabidiol(CBD) is active against a multi-drug resistant bacteria Gram-negativebacteria, P. aeruginosa bacteria, and thus can be useful for preventingor decreasing the extent of the virulence of this bacteria for exampleby inhibiting the biofilm formation and the production of virulencefactors. Therefore, CBD can provide an effective agent for preventionand/or treatment of infections or contaminations caused by bacterialbiofilm forming multi-drug resistant bacteria.

An aspect of the invention provides CBD or a composition thereof for useas a selective antibacterial agent against P. aeruginosa, in particularas an inhibitor of biofilm formation by the said bacteria.

Another aspect of the invention relates to CBD or a composition thereoffor use in the prevention and/or treatment of a disease caused by P.aeruginosa bacteria, in particular in the prevention and/or treatment ofa disease or disorder selected from the group consisting ofhospital-acquired infection, respiratory tract infections, skin and softtissue infections, wound infections, dental and buccal infections,otorhinolaryngologic infections, urological and/or prostatic trackinfections, gastrointestinal infections, biliary tract infection, eyeinfections, bacteremia, sepsis, central nervous system infections andendocarditis.

An aspect of the invention provides a use of CBD or a compositionthereof for the preparation of a pharmaceutical preparation for theprevention and/or treatment of a disease caused by P. aeruginosabacteria, in particular in the prevention and/or treatment of a diseaseor disorder selected from the group consisting of hospital-acquiredinfection, respiratory tract infections, skin and soft tissueinfections, wound infections, dental and buccal infections,otorhinolaryngologic infections, urological and/or prostatic trackinfections, gastrointestinal infections, biliary tract infection, eyeinfections, bacteremia, sepsis, central nervous system infections andendocarditis.

Another aspect of the invention relates to the use of CBD, or acomposition thereof as a sterilizing and/or decontamination agent, inparticular as a sterilizing and/or decontamination agent for medicalmaterial, rooms intended for medical, aesthetic or hygiene practice orfor preparations intended for human or veterinary use.

In a particular embodiment, is provided a use of CBD or a compositionthereof for conservation of work of art.

Another aspect of the invention relates to a decontaminating compositioncomprising CBD, in particular comprising CBD at a concentration betweenabout 0.1 μg/mL to 200 mg/mL, for example from about 0.1 μg/mL to 1mg/mL, in particular from 0.1 μg/mL to 50 μg/mL, more particularly from1 μg/mL to 50 μg/mL and a further physiologically acceptable carrier,diluent or excipient.

Another aspect of the invention relates to a sterilizing compositioncomprising CBD, in particular comprising CBD at a concentration betweenabout 0.1 μg/mL to 200 mg/mL, for example from about 0.1 μg/mL to 1mg/mL, in particular from 0.1 μg/mL to 50 μg/mL, more particularly from1 μg/mL to 50 μg/mL and a further physiologically acceptable carrier,diluent or excipient.

Another aspect of the invention relates to a food, beverage or acosmetic preparation comprising CBD or a decontaminating compositionaccording to the invention.

Another aspect of the invention relates to an article coated with CBD ora composition thereof, in particular an article for use in medical,aesthetic or hygiene practice or in contact with preparations intendedfor human or veterinary use.

According to another aspect of the invention, is provided a kit fordecontamination (e.g. of material surfaces or solutions) or sterilizingcomprising CBD a composition thereof according to the invention, andoptionally instructions for use.

Another aspect of the invention relates a method of sterilization and/ordecontamination of medical material, rooms intended for medical,aesthetic or hygiene practice or preparations intended for human orveterinary use comprising the step of contacting said material, rooms orpreparations with CBD, or a composition thereof, in particular with CBD,or a composition thereof, at a concentration between about 0.1 μg/mL to200 mg/mL.

According to another aspect, is provided a method of preventing orinhibiting P. aeruginosa virulence or the formation of a biofilmthereof, said method comprising contacting a surface or a tissuesusceptible to be contaminated by P. aeruginosa bacteria with CBD, or acomposition thereof, in particular with CBD, or a composition thereof,at a concentration between about 0.1 μg/mL to 200 mg/mL.

According to another aspect, is provided a method of inhibitingvirulence of P. aeruginosa bacteria and/or biofilm formation by saidbacteria, in particular an ex vivo method, said method comprising thestep of contacting a material or a solution containing said bacteriaand/or biofilm thereof with CBD, or a composition thereof.

Another aspect of the invention relates to a method for preventingand/or treating of a disease caused by P. aeruginosa bacteria, inparticular a disease or disorder selected from the group consisting ofhospital-acquired infection, respiratory tract infections, skin and softtissue infections, wound infections, dental and buccal infections,otorhinolaryngologic infections, urological and/or prostatic trackinfections, gastrointestinal infections, biliary tract infection, eyeinfections, bacteremia, sepsis, central nervous system infections andendocarditis, said method comprising administering a therapeuticallyeffective amount of CBD, or a composition thereof according to theinvention, to a subject in need thereof, in particular where CBD, or acomposition thereof is at a concentration between about 0.1 μg/mL to 200mg/mL, for example from about 0.1 μg/mL to 1 mg/mL, in particular from0.1 μg/mL to 50 μg/mL, more particularly from 1 μg/mL to 50 μg/mL.

Another aspect of the invention relates a method for conservation ofwork of art, such as paintings and antique manuscripts, comprising thestep of contacting said work of art with CBD, or a composition thereof.

DESCRIPTION OF THE FIGURES

FIG. 1 shows the relative elastase enzymatic activity of eleastaseproduced by P. aeruginosa PAOW1(PT5) (wt) incubated in the presence ofCBD at 500 μg/ml as described in Example 2 compared to the enzymaticactivity of elastase from the wt or from the wt or from P. aeruginosaΔlasIΔrhII mutant in absence of CBD.

FIG. 2 shows the fold induction (FI) of the expression of genes that arerelated to P. aeruginosa's quorum sensing system in presence of CBD asdescribed in Example 3.

DETAILED DESCRIPTION OF THE INVENTION

The term “hospital-acquired infection (HAI)” or “nosocomial infection”refers to an infection that is contracted from the environment or staffof a healthcare facility (e.g. hospital, nursing home, rehabilitationfacility, clinics). Main routes of infection spread comprise contacttransmissions (e.g. during patient-care activities that require directpersonal contact, contaminated instruments, needles, gloves ordressings), droplet or airborne transmissions, common vehicletransmission (e.g. contaminated food, water, medications, devices andequipment). In some cases, the microorganism originates from thepatient's own skin or gut microbiota, becoming opportunistic aftersurgery or other procedures that compromise the protective skin or gutbarrier, and although the patient may have contracted the infection fromtheir own skin or gut, the infection is considered nosocomial as itdevelops in the health care setting.

The term “virulence factors” are molecules produced by bacteria thatcontribute to the pathogenicity thereof such as adhesins, invasins andantiphagocytic factors for colonization of the host or toxins,hemolysins and proteases, which damage the host.

The term “biofilm”, as used herein, refers to a structured group ofmicroorganisms in which cells adhere to each other and often these cellsadhere to a surface. P. aeruginosa, like some other gram-negativebacteria, grows in the form of aggregates called structured biofilmswherein the cells are coated with a complex matrix composed ofextracellular polymers.

The term “quorum sensing (QS)” refers to a mechanism leading to aregulation of gene expression in response to fluctuations incell-population density. Quorum sensing bacteria produce and releasechemical signal molecules (autoinducers) that increase in concentrationas a function of cell density and a detection of a threshold stimulatoryconcentration of an autoinducer leads to an alteration in geneexpression. A variety of different molecules can be found as signals andinclude oligopeptides N-Acyl Homoserine Lactones (AHL) and a family ofautoinducers known as autoinducer-2 (AI-2) in gram-negative bacteria.Quorum sensing can occur within a single bacterial species as well asbetween diverse species. Bacteria use quorum sensing communicationcircuits to regulate a diverse array of physiological activities andthese include symbiosis, virulence, competence, conjugation, antibioticproduction, motility, sporulation, and biofilm formation. Pseudomonasaeruginosa possesses two known quorum sensing systems based on acylhomoserine lactone (AHL) molecules that are the las system and the rhlsystem and a quinolone-based system. The las system consists of thetranscriptional activator LasR and the AHL synthase LasI, which directsthe synthesis of N-3-oxo-dodecanoyl-homoserine lactone (3-oxo-C₁₂-HSL).The rhl system consists of the transcriptional regulator RhlR and theAHL synthase RhlI, which directs the synthesis of N-butanoyl-homoserinelactone (C₄—HSL). The las system is considered as a key factor in thematuration and differentiation of biofilm, and the rhl system isresponsible for the production of biosurfactants (rhamnolipids) that arenecessary for maintaining an open channel system in Pseudomonas biofilm.Further, quinolone-based system is based on a signaling molecule2-heptyl-3-hydroxy-4-(1H)-quinolone (referred to as Pseudomonasquinolone signal) (Juhas et al., 2005, supra; Masák et al., 2014,supra).

The term “quorum sensing inhibition” refers to inhibition or attenuationof the process of quorum sensing. The inhibitory activity of agents ofthe virulence of bacteria via an action on the quorum sensing mechanismcan be for example assessed indirectly by their effect on biofilmformation (e.g. by measuring read outs of the biofilm mass such asstaining, DNA-quantification confocal laser scanning microscopy toanalyze the morphology of the biofilm) or more directly on the quorumsensing signalling components such as by quantification of mRNA levelsof genes involved in the quorum sensing signaling and virulence factors(e.g. assays for AHL (N-Acyl Homoserine Lactones) production, QS geneactivity, virulence factor production (Las A, LasB, and pyoverdin) andgrowth curve studies and Bradford assay).

Examples of substances acting as a quorum sensing inhibitor includeagents that decrease the production of signaling molecules or inhibitingreceptors thereof.

The term “antiseptic compound” refers to a substance that inhibits thegrowth and the development of microorganisms.

The term “sterilization” refers to the process of elimination ofmicrobiological organisms to achieve asepsis (a sterile microbialenvironment).

The term “decontamination” refers to the process of cleansing an objector substance to remove contaminants comprising bacteria in order toprevent the spread of bacteria.

The term “contamination” of a surface material, a room surface (e.g.walls, floor or room furniture) or sample preparation (e.g. culturemedium, buffer solutions, solubilizing medium, cosmetic, pharmaceuticalor food industrial preparations), refers to the presence of bacteria onthose surfaces or within those preparations at a level that isconsidered to be harmful for the user of such material or samplepreparation either by topical contact, intubation or ingestion. Food ormeal preparations, cosmetic preparation or water can be contaminatedwith Pseudomonas aeruginosa which can rapidly develop within nurturingenvironment (48 h) and cause for example aerobic food degradation.

The term “medical material”, as defined herewith, is any material orpiece of equipment used in healthcare such as in surgery or intensivecare (such as textile for healthcare, paint in healthcare venue,tubings, etc.) piece of equipment designed to aid diagnosis, monitoringor treatment of medical conditions material. It includes catheters (suchas peritoneal dialysis catheters and intravenous catheters),foreign-body implants (such as prosthetic heart valves, cardiacpacemakers, total joint prostheses, renal dialysis shunts), medicalimaging machines (such as ultrasound and MM machines, PET and CTscanners, and x-ray machines), treatment equipment (such as infusionpumps, medical lasers, surgical machines), life support equipment (suchas medical ventilators, anesthetic machines, heart-lung machines, ECMO,and dialysis machines), medical monitors (such as displaying ECG, EEG,and blood pressure), medical laboratory equipment (such as for analysisof blood, urine, genes, and dissolved gases in the blood), diagnosticequipment, therapeutic equipment (such as physical therapy machines),dental equipment (such as dental burs) and contact lenses.

The term “room intended for medical, aesthetic or hygiene practice”encompasses any room where a medical, aesthetic or hygiene act will beperformed on a subject or on sample or material preparation and where acertain degree of asepsis or hygiene is required. Those rooms encompassclean rooms (e.g. medicament, cosmetics or food conditioning rooms),consulting rooms, delivery rooms, emergency rooms, an intensive careunit rooms, maternity wards, nurseries, sickrooms, padded cells, dentisttreatment rooms and operating rooms, aesthetic studios, tanning salonsand the like.

The term “respiratory tract infections (or diseases)” are generallydefined herewith as infectious diseases caused by bacteria, and inparticular a bacteria biofilm, which are involving the respiratory tractand can be classified as upper respiratory tract infections (URI) orlower respiratory tract infection (LRI). Non-limitative examples ofrespiratory tract infections which can be caused by Pseudomonasaeruginosa include pneumonia, bilateral pneumonia with the presence ofmicro-abscesses and tissue necrosis. The term includes all respiratorytract infections that may occur in patients with cystic fibrosis,patients where previously broad-spectrum antibiotic treatment was used,patients where ventilation support equipment is/was used (such asintubation), immuno-compromised patients, patients with prior conditionssuch as chronic lung disease, AIDS or blood cancer (blood cancerpatients mostly develop respiratory tract infections after receivingdrugs), patients with a failure of functioning of the heart pump.

The term “skin and soft tissue infections (or diseases)” are generallydefined herewith as infections or diseases that involve bacterialinvasion of the skin and underlying soft tissues. Examples of skininfections or diseases caused by P. aeruginosa include pyoderma, baby'sand children's pyoderma, gangrene (such as gangrene of the extremities,perineum, face and upper part of the pharynx), diffuse rash accompaniedby vesicles or papules and ecthyma gangrenosum (EG). The term includesall skin infections in subjects with severe burns leading to tissuenecrosis, in subjects after trauma, after skin abrasion (such as scratchand depilation), after contact with contaminated water (such as in steamrooms, jacuzzis and swimming pools), in bedridden subjects and skininflammation due to skin infection (infective dermatitis). Predisposingfactors to skin infection include trauma, pre-existing skin disease,poor hygiene, impaired host immunity (such as leukopenia), and previoustreatment with broad-spectrum antibiotic.

The term “wound infections” and “chronic wound infection” includesinfections such as surgical wound infection, athlete's foot, gramnegative folliculitis, chronic paronychia (green nail syndrome), spapool folliculitis and ecthyma gangrenosum.

The term “urological and/or prostatic track infections” include urinarytract infections such as ecthyma and chronic bacterial prostatitis.Those may occur in subjects after surgeries, for example in patientswith a urinary catheter, or with a disorder of the prostate, or with anyurinary tract obstruction or with an anatomical defect of the urinarytract and in paraplegic patients.

The term “dental and buccal infections” includes dental caries andperiodontitis. The term “otorhinolaryngologic infections” includes earinfections such as otitis externa, which involves the outer ear and earcanal, otitis media, which involves the middle ear and otitis interna(otitis labyrinthitis) and chronic sinusitis. Predisposing factors todevelopment of otitis externa include diabetes and advanced age.

The term “eye infections (or diseases)” includes infections after eyetrauma or after eye contact with contaminated water or contact lenses.

The term “gastrointestinal infections” include biliary tract infection.

The term “bacteremia” refers to the presence of viable bacteria in theblood stream and may occur in subjects with neutropenia, diabetes,burns, malignant hematological diseases and ecthyma gangrenosum.

The term “sepsis” refers to complication of an infection that is apotentially serious medical condition characterized by a whole-bodyinflammatory state (called a systemic inflammatory response syndrome orSIRS) and the presence of either a proven (on the basis of sampling orradiology) or probable (considering the patient's clinical presentation,white cell count, CRP, radiology) infection. The term sepsis summarizesclinical pictures, for which, as a rule, fever, leucocytosis,consciousness changes, a hyperdynamic circulation (“warm shock”), and ahyper-metabolic status, mainly as a consequence of the invasion of thenormally sterile tissue by microorganisms, are observed. The term sepsiscorresponds to the definition of sepsis as defined in the “Definitionsfor Sepsis and Organ Failure and Guidelines for the Use of InnovativeTherapies in Sepsis” from the ACCP/SCCM consensus conference committee(Bone et al., Chest 1992, 101, 1644-1655).

The term “central nervous system (CNS) infections (or diseases)”includes all CNS infections which may occur in subjects after headtrauma, surgery and procedures involving gaining access to CNS such aslumbar puncture or spinal anesthesia. Predisposing factors todevelopment of CNS infections include pre-existing infection,pre-existing disease (such as head and neck cancer), impaired immunesystem and advanced age.

The term “endocarditis” or “infective endocarditis (IC)” refers to aninflammation of the inner layer of the heart, the endocardium, which canalso involve the heart valves, the interventricular septum, the chordaetendineae, the mural endocardium, or the surfaces of intracardiacdevices.

The term “subject” as used herein refers to mammals. For example,mammals contemplated by the present invention include human, primates,domesticated animals such as dogs, cats, cattle, sheep, pigs, horses,laboratory rodents and the like.

As used herein, “treatment” and “treating” and the like generally meanobtaining a desired pharmacological and physiological effect. The effectmay be prophylactic in terms of preventing or partially preventing abacterial infection or a disease, symptom or condition thereof and/ormay be therapeutic in terms of a partial or complete cure of a bacterialinfection, a disease, condition, symptom or adverse effect attributed tothe bacterial infection. The term “efficacy” of a treatment or methodaccording to the invention can be measured based on changes in thecourse of infection, disease or condition in response to a use of acompound or a method according to the invention. For example, theefficacy of a treatment or method according to the invention can bemeasured by its impact on signs or symptoms of infection. A response isachieved when the patient experiences partial or total alleviation, orreduction of unwanted symptoms of infection.

According to one aspect, the efficacy of a treatment according to theinvention can be assessed by the effect of an effective amount of CBD onthe virulence of P. aeruginosa such as an effect on the production ofvirulence factors, on the biofilm formation and/or the quorum sensingsystem of the bacteria. According to a particular aspect, the efficacyof a treatment according to the invention can be assayed by the effect(inhibition/decrease) of the quorum sensing cascade of the bacteria,without necessarily killing it.

The term “effective amount” as used herein refers to an amount of CBD,or a formulation thereof that elicits a detectable reduction of thesymptoms of the disease in a subject that is being administered saidcompound or formulation.

Compounds According to the Invention

The term “cannabidiol (CBD)” refers to a type of cannabinoid that can befound in cannabis plant having the following chemical structure:

2-[(1R,6R)-6-isopropenyl-3-methylcyclohex-2-en-1-yl]-5-pentylbenzene-1,3-diol,also named sΔ²-cannabidiol.

It is a major constituent of the Cannabis plant, second to THC, andrepresents up to 40% in its extracts. Compared with THC has a very lowaffinity for CB1 and CB2 receptors which results in this substance beingnon-psychoactive. CBD can be extracted from various Cannabis plantspecies including Cannabis sativa, indica and ruderalis. In particular,CBD can be extracted as a pure compound from genetically modifiedcannabis plant which is producing increased levels of CBD as compared tonaturally occurring plants.

According to one embodiment, is provided a CBD of a natural origin, thatis extracted from Cannabis strains variety.

According to another embodiment, a CBD can be isolated by standardmethods known to the skilled person, for example comprising collectingof plant material and extraction and purification.

Alternatively, CBD may be prepared by synthetic methods.

Methods and Uses According to the Invention

According to a particular embodiment, are provided CBD or a compositionthereof for use in the prevention and/or treatment of a disease causedby P. aeruginosa bacteria.

In a particular embodiment, the provided CBD or compositions thereof areuseful as an inhibitor of Pseudomonas aeruginosa bacteria.

In a particular embodiment, the provided CBD or compositions thereof areuseful as an inhibitor of biofilm formation by Pseudomonas aeruginosabacteria.

In a more particular embodiment, the provided CBD or compositionsthereof can be useful in the inhibition or decrease of the virulence ofPseudomonas aeruginosa bacteria.

In another particular embodiment, the provided CBD or compositionsthereof can be useful as inhibitors of quorum sensing, in particular ofthe production of virulence factors.

Another particular embodiment provides CBD or a composition thereof foruse in the prevention and/or treatment of a hospital-acquired infectioncaused by P. aeruginosa.

Another embodiment provides CBD or a composition thereof for use in theprevention and/or treatment of a respiratory tract infection caused byP. aeruginosa in patients with cystic fibrosis.

Another embodiment provides CBD or a composition thereof for use in theprevention and/or treatment of infections caused by P. aeruginosa inpatients with burns.

Another embodiment provides CBD or a composition thereof for use in theprevention and/or treatment of infections caused by P. aeruginosa inpatients with chronic wounds.

In a particular embodiment, is provided a use of CBD or a compositionthereof for conservation of work of art such as paintings and antiquemanuscripts.

In a particular embodiment, is provided a use of CBD or a compositionthereof for prevention of contamination with Pseudomonas aeruginosa inpreparations intended for human or veterinary use such as cosmetic,food, beverage or pharmaceutical preparations or for decontamination ofthose. In a more particular embodiment, is provided a use of CBD or acomposition thereof as a sterilizing and/or decontaminating agent.

In a particular embodiment, is provided a use of CBD or a compositionthereof for sterilizing and/or decontaminating medical material, roomsintended for medical, aesthetic or hygiene practice or preparationsintended for human or veterinary use, in particular for decontaminatingor preventing said medical material or preparations from P. aeruginosacontamination.

In a particular embodiment, CBD or a composition thereof is used in thecontext of prevention of food contamination or food decontamination.

In a particular embodiment, CBD or a composition thereof is used in thecontext of prevention of water contamination or water decontamination.

In a particular embodiment, CBD or a composition thereof is used in thecontext of prevention of contamination or for decontamination of medicalmaterial, and/or a room intended for medical, aesthetic or hygienepractice such as medical/hospital rooms, and/or clean rooms.

In a particular embodiment, CBD or compositions thereof or kitsaccording to the invention are useful in a method according to theinvention, in particular a method of inhibiting the virulence of abacteria and/or a method of inhibiting a biofilm formation and/or amethod for preventing and/or treating of a disease caused by Pseudomonasaeruginosa selected from the group consisting of hospital-acquiredinfection, respiratory tract infections, skin and soft tissue infectionsor diseases, chronic wound infection, chronic wound infection, urinarytract infections, ear infections, eye infections, bacteremia, sepsis,central nervous system infections and endocarditis, said methodcomprising administering a therapeutically effective amount of CBD, or acomposition thereof, to a subject in need thereof.

In a particular embodiment, is provided a method for conservation ofwork of art, such as paintings and antique manuscripts, comprising thestep of contacting said work of art with CBD, or a composition thereof.

In a particular embodiment, is provided a method of prevention ofcontamination with Pseudomonas aeruginosa/preservation of preparationsintended for human or veterinary use such as food preparations,beverages, culture or solubilizing media, cosmetic or pharmaceuticalpreparations or of decontamination of those said preparations comprisinga step of contacting said preparations with CBD, or a compositionthereof, in particular with CBD, or a composition thereof, at aconcentration between about 0.1 μg/mL to 200 mg/mL, for example fromabout 0.1 μg/mL to 1 mg/mL, in particular from 0.1 μg/mL to 50 μg/mL,more particularly from 1 μg/mL to 50 μg/mL.

In a particular embodiment, is provided a method of preservation ordecontamination of food or meal preparation.

In a particular embodiment, is provided a method of preservation ordecontamination of beverages or water.

In a particular embodiment, is provided a method of prevention ofcontamination with Pseudomonas aeruginosa of material or rooms intendedfor human or veterinary such as medical material or ofdecontamination/sterilization of those, said method comprising a step ofcontacting said preparations with CBD, or a composition thereof, inparticular with CBD, or a composition thereof, at a concentrationbetween about 0.1 μg/mL to 200 mg/mL, for example from about 0.1 μg/mLto 1 mg/mL, in particular from 0.1 μg/mL to 50 μg/mL, more particularlyfrom 1 μg/mL to 50 μg/mL.

According to a particular embodiment, CBD, or a composition thereof areparticularly suitable for sterilization and/or decontamination ofmedical material.

According to a particular embodiment, CBD, or a composition thereof areparticularly suitable for sterilization and/or decontamination of roomsintended for medical, aesthetic or hygiene practice such asmedical/hospital rooms, and/or clean rooms.

Compositions According to the Invention

Compositions or formulations according to the invention may beadministered as a pharmaceutical formulation.

According to another embodiment, compositions or formulations accordingto the invention are decontamination compositions comprising CBD and atleast one further physiologically acceptable carrier, diluent orexcipient.

Pharmaceutical compositions of this invention may further comprise oneor more pharmaceutically acceptable additional ingredient(s) such asalum, stabilizers, antimicrobial agents, buffers, coloring agents,flavoring agents, adjuvants, and the like.

Compositions of the invention and unit dosages thereof, and in such formmay be employed as solids, such as tablets or filled capsules, orliquids such as solutions, suspensions, emulsions, elixirs, or capsulesfilled with the same, all for oral use, or in the form of sterileinjectable solutions for parenteral (including subcutaneous) use. Suchpharmaceutical compositions and unit dosage forms thereof may compriseingredients in conventional proportions, with or without additionalactive compounds or principles, and such unit dosage forms may containany suitable effective amount of the active ingredient commensurate withthe intended daily dosage range to be employed. According to one aspect,compositions according to the invention are sprayable or inhalable incase of respiratory infections and solutions topically applicable incase of urinary infections.

Compositions of this invention may also be liquid formulationsincluding, but not limited to, aqueous or oily suspensions, solutions,emulsions, syrups, and elixirs. Liquid forms suitable for oraladministration may include a suitable aqueous or non-aqueous vehiclewith buffers, suspending and dispensing agents, colorants, flavors andthe like. The compositions may also be formulated as a dry product forreconstitution with water or other suitable vehicle before use. Suchliquid preparations may contain additives including, but not limited to,suspending agents, emulsifying agents, non-aqueous vehicles andpreservatives.

Suspending agent include, but are not limited to, sorbitol syrup, methylcellulose, glucose/sugar syrup, gelatin, hydroxyethylcellulose,carboxymethyl cellulose, aluminum stearate gel, and hydrogenated ediblefats. Emulsifying agents include, but are not limited to, lecithin,sorbitan monooleate, and acacia. Nonaqueous vehicles include, but arenot limited to, edible oils, almond oil, fractionated coconut oil, oilyesters, propylene glycol, and ethyl alcohol. Preservatives include, butare not limited to, methyl or propyl p-hydroxybenzoate and sorbic acid.

Solid compositions of this invention may be in the form of tablets orlozenges formulated in a conventional manner. For example, tablets andcapsules for oral administration may contain conventional excipientsincluding, but not limited to, binding agents, fillers, lubricants,disintegrants and wetting agents. Binding agents include, but are notlimited to, syrup, accacia, gelatin, sorbitol, tragacanth, mucilage ofstarch and polyvinylpyrrolidone. Fillers include, but are not limitedto, lactose, sugar, microcrystalline cellulose, maizestarch, calciumphosphate, and sorbitol. Lubricants include, but are not limited to,magnesium stearate, stearic acid, talc, polyethylene glycol, and silica.Disintegrants include, but are not limited to, potato starch and sodiumstarch glycollate. Wetting agents include, but are not limited to,sodium lauryl sulfate. Tablets may be coated according to methods wellknown in the art.

Injectable compositions are typically based upon injectable sterilesaline or phosphate-buffered saline or other injectable carriers knownin the art.

Compositions of this invention may also be formulated as suppositories,which may contain suppository bases including, but not limited to, cocoabutter or glycerides. Compositions of this invention may also beformulated for inhalation, which may be in a form including, but notlimited to, a solution, suspension, or emulsion that may be administeredas a dry powder or in the form of an aerosol using a propellant, such asdichlorodifluoromethane or trichlorofluoromethane. Compositions of thisinvention may also be formulated transdermal formulations comprisingaqueous or non-aqueous vehicles including, but not limited to, creams,ointments, lotions, pastes, medicated plaster, patch, or membrane.

Compositions of this invention may also be formulated for parenteraladministration including, but not limited to, by injection or continuousinfusion. Formulations for injection may be in the form of suspensions,solutions, or emulsions in oily or aqueous vehicles, and may containformulation agents including, but not limited to, suspending,stabilizing, and dispersing agents. The composition may also be providedin a powder form for reconstitution with a suitable vehicle including,but not limited to, sterile, pyrogen-free water.

Compositions of this invention may also be formulated as a depotpreparation, which may be administered by implantation or byintramuscular injection. The compositions may be formulated withsuitable polymeric or hydrophobic materials (as an emulsion in anacceptable oil, for example), ion exchange resins, or as sparinglysoluble derivatives (as a sparingly soluble salt, for example).

Compositions of this invention may also be formulated as a liposomepreparation. The liposome preparation can comprise liposomes whichpenetrate the cells of interest or the stratum corneum, and fuse withthe cell membrane, resulting in delivery of the contents of the liposomeinto the cell. Other suitable formulations can employ niosomes. Niosomesare lipid vesicles similar to liposomes, with membranes consistinglargely of non-ionic lipids, some forms of which are effective fortransporting compounds across the stratum corneum.

The compounds of this invention can also be administered in sustainedrelease forms or from sustained release drug delivery systems. Adescription of representative sustained release materials can also befound in the incorporated materials in Remington's PharmaceuticalSciences.

Alternatively, compositions of this invention may also be formulated asan aerosolable solution or an inhalable pharmaceutically acceptablecomposition, e.g. suitable for prevention and/or treatment of pulmonarybacterial infections caused by gram-negative bacteria. In such aformulation, CBD is prepared for example as an inhalable dry powder oras an aerosolable solution.

The compositions according to the invention, together with aconventionally employed adjuvant, carrier, diluent or excipient may beplaced into the form of pharmaceutical compositions and unit dosagesthereof, and in such form may be employed as solids, such as tablets orfilled capsules, or liquids such as solutions, suspensions, emulsions,elixirs, or capsules filled with the same, all for oral use, or in theform of sterile injectable solutions for parenteral use by injection orcontinuous infusion, or in the form of cream, ointment, gel, paste orpowder for topical use.

According to a particular embodiment, compositions of the invention areveterinary compositions.

According to a particular embodiment, compositions of the invention arehand-washing solutions, in particular hand-washing solutions for medicalpersonnel.

According to an aspect of the invention, formulations according to theinvention may be associated with or integrated within an article,notably where time-release and/or mechanical-release of the compositionsis achieved, when the article is placed on an appropriate body part orin an appropriate body cavity.

According to another aspect of the invention, CBD or a compositionthereof are coated on the surface of an article, in particular anarticle for use in medical, aesthetic or hygiene practice or in contactwith preparations intended for human or veterinary use.

According to another aspect, the uses and methods according to theinvention for preventing Pseudomonas aeruginosa infections or disorders,comprise a step of coating an apparatus and materials used in healthcareand notably intensive care and surgery (such as textile, surgicalmaterial, tubings, ventilators, etc.) by a composition comprising CBD.Typically, the composition comprising CBD is incorporated into thesurface or sprayed onto the surface of the said apparatus and materialsused in in healthcare, in particular intensive care and surgery. Furthermaterials as well as formulation processing techniques and the like areset out in Part 5 of Remington's “The Science and Practice of Pharmacy”,22^(nd) Edition, 2012, University of the Sciences in Philadelphia,Lippincott Williams & Wilkins, which is incorporated herein byreference.

Combination

According to the invention, compounds and compositions according to theinvention, and pharmaceutical formulations thereof may be administeredalone or in combination with at least one co-agent useful forcontamination prevention or decontamination.

According to a particular aspect, co-agents according to the inventioninclude antiseptic compound and an antibiotic.

According to the invention, the compounds and compositions according tothe invention, and pharmaceutical formulations is administeredsimultaneously with said co-agent can be administered in the same ordifferent composition(s) and by the same or different route(s) ofadministration.

Mode of Administration

Compositions of this invention may be administered in any mannerincluding, but not limited to, orally, parenterally, transdermally,transmucosally, topically, via inhalation, via buccal or intranasaladministration or intra bladder, or combinations thereof.

Parenteral administration includes, but is not limited to, intravenous,intra-arterial, intra-peritoneal, subcutaneous, intramuscular andintra-cardiac.

Compositions of this invention may also be administered topically to theskin, the ear and the eye.

Compositions of the invention may be administered systemically orlocally.

Compositions according to this invention may also be administered in theform of an implant, which allows slow release of the compounds andformulations thereof as well as a slow controlled i.v. infusion.

Compositions according to the invention may be administered to a subjectin need thereof as a single or as a repeated administration.

Compositions according to this invention may be administered to asubject in need thereof prior to, simultaneously or sequentially withother therapeutic regimens.

The dosage administered, as single or multiple doses, to an individualwill vary depending upon a variety of factors, including pharmacokineticproperties, patient conditions and characteristics (sex, age, bodyweight, health, size), extent of symptoms, concurrent treatments,frequency of treatment and the effect desired.

Patients

In an embodiment, patients according to the invention are subjectsinfected by Pseudomonas aeruginosa or at risk of being infected byPseudomonas aeruginosa.

Predisposing factors to development Pseudomonas aeruginosa includeimpaired host immunity and previous treatment with broad-spectrumantibiotic.

In an embodiment, patients according to the invention are subjects withan altered microbiota.

In an embodiment, patients according to the invention areimmunosuppressed subjects.

In another embodiment, patients according to the invention are patientssuffering from or at risk of suffering from a disease selected from thegroup consisting of hospital-acquired infection, respiratory tractinfections, skin and soft tissue infections, wound infections, dentaland buccal infections, otorhinolaryngologic infections, urologicaland/or prostatic track infections, gastrointestinal infections, biliarytract infection, eye infections, bacteremia, sepsis, central nervoussystem infections and endocarditis.

In a more specific embodiment, patients according to the invention arepatients suffering from or at risk of suffering from a respiratory tractinfection caused by Pseudomonas aeruginosa, such as patients with cysticfibrosis.

In another embodiment, patients according to the invention are patientswith wounds.

In another embodiment, patients according to the invention are patientswith burns.

In another embodiment, patients according to the invention are patientswith foreign-body implants and/or catheters or who will undergo a bodyimplant or catheter surgery.

In an embodiment, patients according to the invention are subjects atrisk of infections caused by bacteria resistant to antibiotics, whichare used in the animal breeding.

Kits

According to one aspect, the invention relates to a kit for carrying outa method according to the invention.

According to another aspect of the invention, is provided a kit fordecontamination, in particular for decontamination of material surfacesor preparations, comprising CBD a composition thereof according to theinvention, and optionally instructions for use.

According to another further embodiment, a kit according to theinvention further comprises at least one antiseptic compound.

According to another further embodiment, a kit according to theinvention further comprises at least one anti-virulence factor agent.

According to another further embodiment, a kit according to theinvention comprising one or more sets of containers, wherein each singleuse set of containers comprises: a first container comprising CBD inlyophilized form or as a liquid formulation and a second containercomprising sterilized tools for decontamination.

According to a particular aspect, formulations, kits and methods of theinvention can be useful in the fields of conservation of work of art,cosmetic, food or beverage preparation decontamination/preservation ormedical material or rooms cleaning or decontamination.

References cited herein are hereby incorporated by reference in theirentirety. The present invention is not to be limited in scope by thespecific embodiments and drawings described herein, which are intendedas single illustrations of individual aspects of the invention, andfunctionally equivalent methods and components are within the scope ofthe invention.

EXAMPLES

The following abbreviations refer respectively to the definitions below:

-   -   CBD (cannabidiol); CV (crystal violet); lasB (gene encoding LasB        Elastase); lasI (gene encoding C12 autoinducer synthase); OD₆₀₀        (optical density measured at a wavelength of 600 nm); pqsH (gene        involved in quinolone autoinducer synthesis); rhlA (gene        involved in rhamnolipids synthesis); rhlI (gene encoding C4        autoinducer synthase); wt (wild type).

Example 1: Reduction of Biofilm Formation of Pseudomonas aeruginosa byCBD

The effects of CBD on P. aeruginosa biofilm formation was assessed asdescribed below.

Overnight pre-cultures of Pseudomonas aeruginosa ATCC 27853 strain werediluted to an OD₆₀₀ (optical density measured at a wavelength of 600 nm)of 0.1 in 2 ml of LB (lysogeny broth) medium into polypropylene tubes.Tubes containing bacteria and CBD at concentrations of 1.9 μg/ml, 3.9μg/ml, 7.8 μg/ml, 15.63 μg/ml, 31.25 μg/ml, 62.5 μg/ml and 125 μg/mlwere incubated for 12 h at 37° C. without shaking. Planktonic cells wereremoved by washing once with distilled water and biofilms were stainedwith crystal violet (CV, 1% in water) for 30 minutes. CV was discardedand tubes were rinsed twice with water to remove excess of dye. Thestained biofilms were re-suspended in 33% acetic acid and their densitywas evaluated by measuring the OD₆₀₀ of the suspensions normalized forbacterial density.

Measurement of biofilm formation of Pseudomonas aeruginosa ATCC 27853 inthe presence of CBD showed that CBD at concentrations between 1.9 μg/mlto 31.25 μg/ml can reduce by the factor of about 2 the biofilm formationas compared to control without CBD.

At higher concentration of CBD, the inhibitory effect on biofilmformation is reduced probably due to the reduced solubility of CBD inthe culture medium.

Example 2: CBD-Induced Reduction of Virulence Factors Production byPseudomonas aeruginosa

The effect of CBD on the production of elastase by P. Aeruginosa, avirulence factor whose expression is directly regulated by the quorumsensing system, was assessed through the measurement of the elastaseenzymatic activity.

Elastase production was measured in two bacterial strains: Pseudomonasaeruginosa PAOW1(PT5) that is a wild type (wt) and Pseudomonasaeruginosa ΔlasIΔrhII that is a mutant for quorum sensing signaling thathas reduced production/expression of elastase due to the inhibition ofthe quorum sensing system. 100 μl of filtered bacterial supernatant ofovernight cultures (with or without 500 μg/ml of CBD, where cultureswere under shaking that allows better CBD dispersion) were added to 900μl of Elastin Congo Red (ECR) buffer (100 mM Tris, 1 mM CaCl₂, pH 7.5containing 20 mg of Elastin ECR) and then incubated with shaking at 37°C. for 3 h. Insoluble ECR was removed by centrifugation and theabsorption of the supernatant was measured at 495 nm and normalizedaccording to cell density.

The enzymatic activity of the elastase produced by P. aeruginosaPAOW1(PT5) in presence of CBD showed that CBD at a concentration of 500μg/ml can reduce by about 30% the production of elastase as compared tocontrol values (FIG. 1 ). The production of elastase by P. aeruginosaΔlasIΔrhII is reduced by about 93% as compared to control (production ofelastase by wt).

These results indicate that CBD can effectively reduce the production ofat least some P. aeruginosa virulence factor involved in the quorumsensing system.

Example 3: CBD-Induced Modulation of Expression of Genes Involved inQuorum Sensing of Pseudomonas aeruginosa

The effects of CBD on P. aeruginosa's quorum sensing system wereassessed through the expression of genes related to quorum sensing.

Overnight pre-cultures of Pseudomonas aeruginosa PAOW1(PT5) (wt) werediluted to an OD₆₀₀ of 0.05 and grown for 6 hours at 37° C. with orwithout 500 μg/ml of CBD. 0.5 ml of cultures were added to 1 ml of RNAProtect bacteria solution and total RNA was isolated with RNeasy columns(Qiagen). Residual DNA was eliminated by DNase treatment using 20 unitsof RQ1 RNase-free DNase (promega). After removal of DNase byphenol/chloroform extraction and precipitation, 500 ng of RNA wasreverse-transcribed using random hexamer primers and Improm-II reversetranscriptase (promega). 2.5 μl of 10-fold diluted cDNA were quantifiedby real-time PCR (qPCR) using a Sybr Select Master Mix for CFX (4472942)(Thermofisher). Primers, start in gene (bp) and amplicon size (bp) usedare listed in the Table 1. Each amplification was normalized by theinternal standard (oprF) value of the corresponding cDNA (complementaryDNA). The results are expressed as fold increase compared to the wtcultivated without CBD. The following genes' expression has beenmeasured: rhII encoding C4 autoinducer synthase; rhlA that is a geneinvolved in rhamnolipids synthesis, lasI encoding C12 autoinducersynthase, lasB encoding LasB Elastase and pqsH that is a gene involvedin quinolone autoinducer synthesis.

TABLE 1 start in gene amplicon gene primer sequence (bp) size (bp) rhlI309 SEQ ID NO: 1: CTCTCTGAATCGCTGGAAGG 13 240 310 SEQ ID NO: 2:GACGTCCTTGAGCAGGTAGG 252 rhlA 299 SEQ ID NO: 3: CGAGGTCAATCACCTGGTCT 279208 300 SEQ ID NO: 4: GACGGTCTCGTTGAGCAGAT 486 lasI 311 SEQ ID NO: 5:CTACAGCCTGCAGAACGACA 390 168 312 SEQ ID NO: 6: ATCTGGGTCTTGGCATTGAG 557lasB 301 SEQ ID NO: 7: AAGCCATCACCGAAGTCAAG 260 230 302 SEQ ID NO: 8:GTAGACCAGTTGGGCGATGT 489 pqsH 303 SEQ ID NO: 9: ATGTCTACGCGACCCTGAAG 629169 304 SEQ ID NO: 10: AACTCCTCGAGGTCGTTGTG 797

The fold induction of expression of genes by P. aeruginosa PAOW1(PT5)incubated in the presence of CBD (500 μg/ml) was 1.46 for rhII, 0.72 forrhlA, 0.89 for lasI, 0.42 lasB and 0.53 for pqsH as compared to controlconditions (FIG. 2 ) which indicates that CBD is able to affect thePseudomonas aeruginosa virulence by interfering with the quorum sensingsystem.

I claim:
 1. A method of sterilization and/or decontamination of medicalmaterial, rooms intended for medical, aesthetic or hygiene practice orpreparations intended for human or veterinary use from P. aeruginosacontamination, said method comprising the step of contacting saidmaterial, room or preparations with CBD, or a composition thereof. 2.The method according to claim 1, wherein said preparation is selectedfrom a cosmetic preparation, food, meal preparation or beverage.
 3. Themethod according to claim 1, wherein said material is medical material.4. The method according to claim 1, wherein said room is selected frommedical, hospital or clean rooms.
 5. The method according to claim 1,wherein said CBD is at a concentration between about 0.1 μg/mL to 200mg/mL.
 6. The method according to claim 1, wherein said material, roomor preparations contain P. aeruginosa bacteria and wherein the virulenceof P. aeruginosa bacteria and/or biofilm formation by said bacteria isinhibited.
 7. The method according to claim 6, wherein the CBD is at aconcentration between about 0.1 μg/mL to 200 mg/mL.
 8. A decontaminatingor sterilizing liquid composition comprising CBD at a concentrationbetween about 0.1 μg/mL to 200 mg/mL and a physiologically acceptablecarrier, diluent or excipient.
 9. A food, beverage or a cosmeticpreparation comprising CBD or a composition thereof as preservative orsterilizing agent of said preparation at a concentration of about 1μg/mL to 50 μg/mL.
 10. An article coated with CBD or a compositionthereof, wherein said article is selected from a textile, a surgicalmaterial, tubing, catheter, prosthetic heart valve, cardiac pacemaker,total joint prosthesis, renal dialysis shunt, and a ventilator.
 11. Akit for material surface or solution decontamination or sterilizing fromP. aeruginosa contamination comprising CBD or a composition thereof, andoptionally instructions for use comprising a decontaminating orsterilizing composition according to claim 8.